L14_T Cell Developement Flashcards
Where does T-cell maturation take place?
The thymus
What is the embryonic origin of the thymus?
The 3rd pharyngeal pouch and cleft
Where do T-cell precursors originate from?
The liver and bone marrow
What is thymic anlage?
The tissue from which the thymic stroma develops during embryogenesis
What is the thymic stroma?
epithelial cells and connective tissue that form the essential microenvironment for T-cell development
Where to T-cell progenitors enter the thymus?
At the cortico-medullary junction
Where do cells that survive selection exit the thymus?
From venules in the medulla (controlled by chemokines and sphingosine 1 phosphate receptors.
What TCR chains begin rearrangement during the double negative phase?
Beta, Gamma, and Delta
In the double negative stage, what fraction of cells are triple negative?
2/3
At what stage does TCR alpha rearrangement begin?
Double Positive
Which subset of thymocytes is most sensitive to apoptosis?
Double Positive
What is the rough ratio of CD4 to CD8 T-Cells?
2:1
En route to the DP stage, which CD marker gene is turned on first, CD4 or CD8?
CD4
What are the two checkpoints involved in alpha beta T cell development?
First Checkpoint: Mediated by pre TCR (also referred to as beta selection)
Second Checkpoint: Mediated by mature alpha/beta TCR (also referred to as positive and negative selection)
What is the purpose of the first checkpoint in alpha/beta TCR development? What are the consequences?
To assess whether TCRbeta chain is functionally rearranged. If pTCRbeta is successfully express there is allelic exclusion at the TCRbeta locus, proliferation, expression of CD4 and CD8, termination of transcription at gamma locus, initiation of rearrangement at alpha locus.
What is the purpose of the second checkpoint in alpha/beta TCR development?
1 to asses whether TCR alpha is functionally rearranged 2 to assess whether TCR is self MHC restricted 3 to assess whether TCR is autoreactive.
How do most DP cells in the thymus die?
Death by neglect.
What APC are used in the thymus for selection?
hematopoietic cells (dendritic) and stromal cells (Cortical and medullary epithelial cells)
Where are peptides present on APCs in the thymus derived?
endogenous sources in the thymus or serum components
How are T-cells that are self reactive with peripherally expressed antigens negatively selected for in the thymus?
A protein called AIRE causes epithelial cells in the thymus to transcribe, translate, and degrade tissue specific peripheral proteins to be presented by APCs in the thymus.
What are the only cells that can induce positive selection?
Cortical epithelial cells
What cells can induce negative selection, which cannot?
thymic dendritic cells, cortical epithelial cells, medullary epithelial cells can all induce negative selection. Thymic Macrophages cannot induce negative selection, their only job it to eat up all the dead cells.
